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Development of the Cardiovascular System — Introduction
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The development of the cardiovascular system is an early embryological event. It begins
during the third week of gestation or the fifth week LMP.
From fertilization, it takes five weeks for the human heart to develop into its definitive
fetal structure. During this period, the system develops so it can:
- Supply nutrients and oxygen to the fetus
- Immediately function after birth
The heart first begins as a horseshoe shaped pericardial cavity with an inner endocardial
tube. This endocardial heart tube is then surrounded by visceral mesoderm which will
become the myocardial mantle. The two endocardial heart tubes fuse and the fused
single heart tube begins to beat at approximately 21 days of gestation.
Then the heart tube convolutes and a primitive heart is established the end of the first
month of gestation or 6 weeks LMP. This heart can be described as having three regions:
an inflow tract, the cardiac chambers, and an outflow tract.
Finally, the heart undergoes septation and the four chambers of the heart are established
by 37 days after gestation or 7 weeks LMP.
Early Development of the Circulatory System
Cardiac Muscle Cells
During gastrulation, the cells that will give rise to the heart move to an anterior and
lateral position of the mesoderm.
It appears that signals from the endoderm may cause the expression of cardiac specific
genes that allow for the differentiation of mesodermal cells into cardiac muscle cells.
BMP2,4 in the endoderm and crescent, a WNT inhibitor, are co-expressed and where
they overlap induce NKX2.5 in the mesoderm which is necessary for heart induction.
Very early in development the cardiac muscle cells are organized in a cephalo-caudal
direction.
The more cephalic cells will become the outflow tract of the heart and the more caudal
cells will be located at the inflow region.
Heart Tube
In the embryo, a horseshoe-shaped prospective pericardial cavity is located in a
precephalic position, rostral to the oral and neural plate.
By the middle of the third week of gestation cardiac muscle cells in the visceral
(splanchnic) mesoderm form a plexus of vessels
which develop into a horseshoe-shaped endocardial
heart tube. These vessels lie deep to the pericardial
cavity.
The lateral plate visceral mesoderm proliferates,
surrounds the endocardial heart tubes, and develops
into the myocardium.
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The epicardium develops from cells that migrate over the myocardial mantle from areas
adjacent to the developing heart.
The heart tube consists of an endocardial layer surrounded by the myocardium with an
intervening layer of extracellular matrix, sometimes called the cardiac jelly.
The cephalic ends of the endocardial heart tubes connect in the midline and also connect
via aortic arches, with a pair of newly forming vessels, the dorsal aortae, located on
either side of the midline.
The caudal ends of these endocardial heart tubes continue to develop and soon connect to
the umbilical veins developing in the yolk stalk.
As the embryo undergoes lateral body folding, head and tail folding, and cephalic growth
of the brain, there is a shift of the endocardial heart tubes medially, ventrally and
caudally. They fuse in the midline as a single endocardial heart tube. The resulting
heart tube is suspended in the pericardial cavity by the dorsal mesocardium.
When the single heart tube is formed, the embryo is at the beginning of the fourth week
of gestation, is about 3 mm in length, has 4 - 12 somites, and the neural tube is beginning
to form. The heart now begins to beat.
Vascular Circuits
As the heart begins to beat, blood islands coalesce to form three vascular circuits.
Within the embryo an embryonic circuit forms. It consists of paired dorsal aortae that
arise from the endocardial heart tube and break up into capillary networks that supply
blood to the developing embryonic tissues. Blood is drained from these tissues by
anterior and posterior cardinal veins that drain into common cardinal veins, which in
turn drain into the endocardial heart tube.
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Two extraembryonic circuits also form.
1. The first is the vitelline circuit. In this circuit, blood from the dorsal aortae flows
into vitelline arteries that supply the yolk sac. The blood drains back to the heart
tube via paired vitelline veins.
2. The second extraembryonic circuit is the umbilical circuit. Here the dorsal aortae
supply blood to umbilical arteries that in turn bring this now deoxygenated blood
back to the placenta. Blood from the placenta is carried to the heart tube via
umbilical veins.
Formation of the Primitive Four Chambered Heart
Heart Tube Dilation
As the endocardial heart tube fuses, several bulges and sulci
appear. From the caudal to the cephalic end, the bulges are:
- Sinus venosus. This is the inflow tract of the heart
tube. Blood flows into the sinus venosus via the veins.
- Primitive atrium
- Primitive ventricle
- Bulbus cordis, which consists of the aortic sac, the
truncus arteriosus and the conus arteriosus. This is
the outflow tract of the heart tube. Paired dorsal aortae
arise from aortic arches that in turn arise from the
aortic sac. The aortic sac is at the most cephalic end
of the bulbus cordis.
The sulci present are the bulboventricular sulcus, between the
bulbus cordis and the ventricle, and the atrioventricular
sulcus, between the atrium and the ventricle.
Looping
There now occurs a rapid growth of the heart tube and the heart begins to loop anteriorly
and to the right. This is important for the proper alignment of the inflow and outflow tracts
with the cardiac chambers.
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During the process of convolution, the first flexure seen is between the bulbus cordis and
the ventricle. The bulboventricular loop shifts this region of the heart to the right and
ventrally.
The second flexure, atrioventricular loop, is between the atrium and the ventricle and
this region of the heart is shifted to the left and dorsally.
As growth continues, the atria shift cephalically and begin to bulge forward on either side
of the bulbus cordis, shifting the bulbus medially. The sinus venosus shifts to the right to
empty into the right atrium.
During convolution, the dorsal mesocardium begins to degenerate, leaving a space that
becomes the transverse sinus.
The atrioventricular canal is the opening that remains after convolution of the heart
tube, which connects the primitive atrium to the primitive ventricle. The canal shifts to
the right during the stages after convolution. Initially, the common atria are located over
the primitive ventricle. However, there is a shifting of the AV canal to the right that
subsequently aligns the atria over the bulbus cordis and primitive ventricle. The AV
canal is then separated into a right and left side.
The bulboventricular sulcus is represented inside the heart as the bulboventricular
flange. The bulboventricular flange and the muscular interventricular septum separate
the primitive ventricle (which will become the left ventricle) from the conus arteriosus
(which will become the definitive right ventricle). The bulboventricular flange later
regresses leaving a cephalically located hole in the IV septum, called the IV foramen.
Heart Tube Dilatation
Truncus arteriosus
Conus Arteriosus
Primitive Ventricle
Primitive Atrium
Sinus Venosus
Pulmonary Vein
Adult Structure
Aorta and Pulmonary Artery
Right Ventricle
Left Ventricle
Trabeculated Portion of Left and Right Atrium
Smooth Portion of Right Atrium, Coronary
Sinus, Oblique Vein of Marshall
Smooth portion of Left Atrium
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Mechanisms of Looping
The mechanism for this convolution process is not well understood. However it is clear
there is an asymmetric expression of different cell-cell signaling molecules. For
example, Nodal is expressed on the left side with Snr1 expressed on the right. How this
relates to looping is unknown. Looping is one of the first examples of asymmetry within
the embryo.
It does appear that the cytoskeleton is important in the looping process. Recent evidence
suggests that early in development, cells in the cardiac region with defective cilia will not
convolute properly. Thus early on cilia help establish a gradient within the extracellular
matrix that guides the convolution process.
Septation of the Heart
During the second month, the heart begins to undergo septation into two atria, two
ventricles, the ascending aorta and the pulmonary trunk.
Atrial Septation
Formation of the Atrioventricular Septum
Endocardial cushions develop in the dorsal (inferior) and ventral (superior) walls of the
cardiac atrioventricular canal.
Specific cells from the endocardium are induced by the myocardial cells and migrate into
the extracellular matrix tissue in between the endocardium and myocardium. These cells
will be found not only in the region of the AV canal but also a similar population of cells
is found in the outflow tract region. These mesenchymal cells will begin to differentiate
along different lines according to the structure that they will develop into.
In the region of the AV canal, one group of the mesenchymal cell population grows and
populates the two cushions which then grow toward each other.
These cushions fuse and divide the common AV canal into the left and right AV canals.
Ventral AV
Cushion
Dorsal AV
Cushion
Formation of the Atrial Septum
As the endocardial cushions develop, there is a developing septum from the dorsocranial
atrial wall that grows toward the cushions. This is the septum primum, and the
intervening space is called the foramen primum.
As the septum reaches the endocardial cushions closing foramen primum, a second
opening, foramen secundum appears in septum primum. This is necessary to permit
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flow of blood from the developing right atrium to the developing left side of the heart.
As foramen secundum enlarges, via apoptosis or programmed cell death, a second
septum, septum secundum forms to the right of septum primum.
Septum secundum forms an incomplete partition (lying to the right of foramen
secundum) that leaves an opening, the foramen ovale. The remaining portions of septum
primum become the valve of foramen ovale.
Right Atrium
Concurrently, the sinus venosus has shifted to the right. The right sinus venosus becomes
incorporated into the right atrium forming the smooth portion of the right atrium.
The primitive right atrium is seen in the adult as the rough portion (auricle) of the right
atrium.
The remainder of the left sinus venosus is the coronary sinus and the oblique vein (of
Marshall) in the adult heart.
Left Atrium
On the left side, the primitive atrium is enlarged by the incorporation of tissue from the
original, single pulmonary vein and its proximal branches. The vein develops in the
mediastinum from blood islands that coalesce. These newly formed vessels branch as
they develop in the developing lung tissue.
In the region of the left atrium, these vessels become reabsorbed into the left atrium and
the tissue is incorporated and becomes the adult smooth left atrial wall. The vessels
become reabsorbed up to the second branch point, which then leaves four pulmonary
veins emptying independently into the left atrial chamber.
The trabeculated left atrial appendage is a remnant of the primitive left atrium.
Ventricular Septation
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The endocardial cushions eventually lie opposite the developing interventricular septum.
The septum is the inward manifestation of the bulboventricular sulcus.
The muscular interventricular (I.V.) septum grows as a ridge of tissue from the caudal
heart wall toward the fused endocardial cushions.
The interventricular foramen is the opening remaining between the muscular IV
septum and the fused endocardial cushions.
This foramen is closed by the membranous part of the interventricular septum, which
is formed by the fusion of tissue from three sources:
- Conal ridges,
- An outgrowth of the inferior endocardial cushion - the right tubercle
- Connective tissue from the muscular interventricular septum
Septation of the Bulbus Cordis
Truncal and conal septa fuse to form an 180o spiral and together definitively form the
aorta and the pulmonary artery.
- Truncal swellings (ridges) appear first as bulges in the truncus on the right
superior and the left inferior walls. They enlarge and fuse in the midline to form
the truncal (aorticopulmonary) septum. This septum separates the distal
pulmonary artery from the aorta.
- At the same time right dorsal and left ventral conal ridges form and fuse in the
midline. The conal septum helps divide the proximal aorta from the pulmonary
artery and contributes to the membranous IV septum.
Cells that contribute to the conal and the truncal septa are in part derived from neural
crest cells that migrate into these regions.
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At this point in development (day 35 of gestation or 7 weeks LMP), the right atrium is in
communication with the conus arteriosus, which is now the right ventricle. The left atrium is in
communication with the primitive ventricle, which is now the left ventricle. The right and left
atria remain in communication via the foramen ovale and ostium secundum. Thus, the
primitive four-chambered heart is formed and blood flows from the veins to sinus venosus, to
atria, to ventricles, to truncus, to aortic sac, and then to dorsal aorta.
Cardiac Valve Formation
Semilunar valves develop in the aorta and pulmonary artery as localized swellings of
endocardial tissue.
The atrioventricular valves develop as subendocardial and endocardial tissues and
project into the AV canal.
These bulges are excavated from the ventricular side and invaded by muscle. Eventually,
the valve will be constituted from both connective tissue and myocardial tissue. In
addition, muscle cells will make up a large part of the papillary muscle which attaches to
the valve leaflets.
The remodeling of the AV canal cushion tissue results in three cusps of the right AV
(tricuspid) valve, and two cusps of the left AV (mitral) valve.
The atrial myocardium is separated from the ventricular myocardium by connective
tissue except in the region of the AV node and bundle.
There are growth factors that are associated with the development of the endocardial
cushions. Growth factors such as members of the Fibroblast Growth Factor and Insulinlike growth factor families as well as other factors such as BMP-2, Smad6, NF-Atc, and
Sox4 may play important roles in the development of the valves and the connective tissue
that separates ventricular and atrial tissue.
The separation of these tissues is important, as extra connections between the atrial and
ventricular chambers can lead to the generation of cardiac arrhythmias.
Development of the Cardiac Conduction System
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The conduction system regulates the electrical activity of the heart. It consists of the
sinoatrial node, the atrioventricular node, the atrioventricular bundle (of His), the left and
right bundle branches, and the Purkinje fibers.
The sinoatrial node and the atrioventricular node develop from regions of the heart tube
that have slow conducting properties. This explains why the AV node is a region where
conduction velocities slow before arriving at the AV bundle.
The AV bundle and the Purkinje fibers arise from fast conducting working myocardium.
These cells are found near the developing coronary vessels and perhaps under the
influence of the growth factor endothelin-1 (ET-1), they differentiate into the bundle
branches and the Purkinje fibers that connect the AV bundle to the working myocardium.
However the exact influences that regulate the development of conduction system are not
known.
Development of the Major Arteries
The six pairs of aortic arches, develop in a cephalo-caudal direction and interconnect the
ventral aortic roots and the dorsal aorta.
They are never all present in the developing human heart. Of the six pairs of aortic
arches, most of the first, second and fifth arches disappear. The fate of the arches, ventral
roots and the dorsal aorta are listed below.
STRUCTURE
RIGHT
LEFT
1st Aortic Arch
Most disappear (some forms
maxillary art.)
Most disappear (some forms
maxillary art.)
2nd Aortic Arch
Most disappears
Most disappears
3rd Aortic Arch
Proximal internal carotid
artery
Proximal internal carotid
artery
Cranial Dorsal Aorta
Distal internal carotid artery
Distal internal carotid artery
Ventral Aorta between 3rd
and 4th Arch
Common carotid artery
Common carotid artery
Ventral Aortic Root to 4th
Arch
Brachiocephalic artery
Ascending aorta
Dorsal Aorta between 3rd
and 4th Arch
Disappears
Disappears
4th Aortic Arch
Proximal right subclavian
artery
Arch of aorta
Dorsal Aorta between 4th
arch and 7th intersegmental
artery
Middle of the subclavian
artery
Distal arch of the aorta
7th intersegmental artery
Distal subclavian artery
Subclavian artery
5th Aortic Arch
Never developed
Never developed
Proximal 6th Aortic Arch
Proximal right pulmonary
artery
Proximal left pulmonary
artery
Distal 6th Aortic Arch
Disappears
Ductus arteriosus
Dorsal Aorta below 7th
Intersegmental artery to the
Junction of the Dorsal Aorta
Disappears
Descending aorta
Development of the Major Veins
The veins develop in a much more variable way than the arteries. An initial anterior and
posterior cardinal system of veins provides venous drainage for the fetus. New
subcardinal veins and supracardinal veins develop as a consequence of the changes found
in the abdomen of the developing embryo.
The formation of the liver and the mesonephric kidney has profound affects in redirecting
blood flow. The enlarging liver encroaches upon the developing vitelline and umbilical
veins and gradually all the blood will drain to the proximal right vitelline vein. The distal
vitelline veins will give rise to the portal system. The left umbilical vein remains and
drains into the ductus venosus, a shunt that allows blood to bypass the developing liver
and which empties into the proximal right vitelline vein.
Superior and Inferior Vena Cava
STRUTURE
RIGHT
Common Cardinal V
Superior Vena Cava
Coronary Sinus
Proximal Ant. Cardinal V
Superior Vena Cava
Superior Intercostal V
Thymicothyroid Anastomosis
LEFT
Brachiocephalic V
Intermediate Ant. Cardinal V
Brachiocephalic V
Degenerates
7th Intersegmental V
Subclavian V
Subclavian V
Distal Anterior Cardinal V
Internal Jugular V
Internal Jugular V
New Vessel
External Jugular V
External Jugular V
Inferior Caval System
Structure
Right
Left
Vitelline V (Proximal)
Proximal IVC and Hepatic V
Hepatic V
Subcardinal V and subcardinal
Anastomosis
IVC (renal portion), Renal,
Gonadal and Suprarenal V
Gonadal, Renal and
Suprarenal V
Hepato-subcardinal
anastomosis
IVC (hepatic segment)
None present
Distal Supracardinal V
IVC (postrenal segment)
Proximal Supracardinal V
Distal Azygos V
Proximal Posterior Cardinal V
Proximal Azygos V
Distal posterior Cardinal V
Right Common Iliac V
Hemiazygos V
Left common iliac V
Portal System
Structure
Right
Left
Proximal Vitelline V
Cephalic IVC & Hepatic V
Hepatic V
Middle Vitelline V
Broken up by Hepatic
Sinusoids
Broken up by hepatic
sinusoids
Vitelline V (caudal to liver
with transverse anastomoses)
Portal V
Portal V
Distal Vitelline V
Superior Mesenteric V
?Splenic V?
Proximal Umbilical V
Degenerates
Degenerates
Distal Umbilical V
Degenerates
Ligamentum Teres
Ductus Venosus
Ligamentum Venosum
Changes at Birth
During development, the fetus receives oxygenated blood from the placenta. This blood
travels through the umbilical veins initially and then after the development of the liver
though the left umbilical vein and the newly formed ductus venosus.
The placental blood bypasses the liver and the ductus venosus empties into the inferior
vena cava. From the inferior vena cava the blood enters the right atrium.
Since the lungs do not function in the fetus, the right atrial pressure is higher than the left
atrial pressure. Blood from the right atrium can empty into the right ventricle or cross the
interatrial septum via the foramen ovale to enter into the left atrium.
The pulmonary arteries bring very little fetal blood to the developing lungs from the right
ventricle. Most of the blood is directed toward the systemic circulation via the ductus
arteriosus, which connects the pulmonary trunk with the arch of the aorta. Blood from
the left atrium also travels to the left ventricle and then to the developing fetal tissues via
the aorta.
At birth the lungs become inflated and oxygen now enters the blood in the lung tissue.
This oxygenation also serves to promote further dilation of the pulmonary vasculature.
The umbilical artery is constricted and this results in the constriction of the ductus
venosus.
Now right atrial pressure is reduced especially in relation to left atrial pressure. The
increased left atrial pressure results in the valve of the foramen ovale, the old septum
primum, becoming pressed against the septum secundum and the communication
between left and right atria becomes eliminated with the formation of an intact interatrial
septum.
Finally, the ductus arteriosus closes. During the fetal period the ductus venosus and
ductus arteriosus remain open, in part due to the presence of prostaglandins, which keep
these vessels dialated.
After birth the elevated oxygen levels plus the release of bradykinins from the lungs, act
to promote the constriction of the ductus arteriosus. This vessel closes during the few
weeks after birth. If the vessel does not close then infants can be given prostaglandin
inhibitors that will close this vessel.
Congenital Abnormalities
The development of the heart is a complex process that requires significant movement of
tissues and changes in relationships of one structure to another. Defects in the heart and the great
vessels can lead to death not only after birth but also in utero. When considering the
development of the heart it is important to keep in mind the normal anatomy. Abnormalities can
be described on the basis of how the normal development may not have occurred properly and
caused these defects.
Atrial Defects
The development of the atria involves the formation of an interatrial septum that arises
from four structures:
1. septum primum,
2. septum secundum,
3. the incorporated sinus venosus, and
4. the endocardial cushion tissue.
Four types of defects can occur that result from the failure of
one or more of these structures to develop normally.
I. The most common interatrial septal defect is the foramen
ovale defect (ostium secundum defect).
This defect (Fig. 1) occurs when ostium secundum
becomes too large as the result of the loss of too
much septum primum tissue.
Another factor also may be too little growth of
septum secundum. This leaves an opening in the
region of fossa ovalis that permits blood flow
between the atria.
Figure 1
II. Another interatrial septal defect that occurs is the upper
interatrial septal defect (sinus venosus defect).
This defect (Fig. 2) occurs when the sinus venosus is not
properly incorporated into the right atrium and interatrial
septum. The sinus venosus may be incompletely
incorporated or else may not shift to the right enough to be
fully incorporated into the septum.
Another possibility is that the septum secundum may not
develop or may become reabsorbed. In either case there is
a defect in the interatrial septum, above the fossa ovalis.
Figure 2
III. A low interatrial septal defect (ostium primum) (Fig. 3)
occurs when there is the retention of the foramen primum.
This may be due to the inadequate growth of septum
primum, or it can be due to a malformation of
endocardial cushion tissue. In either case the
persistence of a lower interatrial foramen occurs.
If endocardial cushion tissue is involved then there
also may be a common atrioventricular canal.
With a common AV canal defect, there also can be
an interventricular septal defect (Fig. 3).
Abnormal valve formation also may accompany this
defect.
Figure 3
IV. Finally, an uncommon interatrial defect is the common atrium or cor triloculare
biventriculare. This defect is the result of the lack of septum primum and septum
secundum formation. An interatrial septum is not present and the atria form one large
chamber.
Ventricular Defects
The interventricular septal defects are common defects of the heart. This is
understandable given the complex movements that are needed for the contribution to this
structure from endocardial cushion tissue, muscular interventricular septal tissue and
aorticopulmonary septal tissue. This is especially true given the shifting and spiraling of the
aorticopulmonary septum during normal development of the heart.
I. The pars membranaceum defect of the interventricular
septum (Fig. 4) occurs as the result of the abnormal contribution
of endocardial cushion tissue, a lack of connective tissue from the
muscular interventricular septum, or the lack of aorticopulmonary
tissue. During discussions of other types of defects it is seen that
this interventricular septal defect is often associated with other
congenital cardiac abnormalities.
II. There can be defects in the muscular interventricular septum.
These are called pars muscularis defects (figure 5). During
normal development there are numerous sinuses or canals between
the two ventricular chambers. Normally they are obliterated with
the final formation of the interventricular septum. However, at
times the interventricular connections remain and an
interventricular defect such as that seen on the right can occur.
Figure 4
III. Finally, there can be interventricular defects that occur with the complete absence of the
interventricular septum. This defect is called cor triloculare biatriatum (figure 6). In this
defect there are two atrial chambers that both empty into a single ventricular chamber.
Figure 6
Figure 5
Bulbus Cordis Defects
I. One type of bulbus cordis defect is the absence of part or all of the aorticopulmonary septum.
In figure 7 the caudal part of the septum is absent so that there is a partial persistent
truncus arteriosus defect.
In figure 8, there is a complete absence of the aorticopulmonary septum so that the
pulmonary arteries arise from the common truncus arteriosus.
In both cases, there is an accompanying IV defect which results from the lack of a
contribution of the bulbar septum to the IV septum.
Figure 8
Figure 7
II. Another type of defect is transposition of the great vessels. This
is due to the improper spiraling of the aorticopulmonary septum.
In figure 9, the defect depicted is transposition of the outflow
tract. Here the aorta arises from the right ventricle and the
pulmonary artery arises from the left ventricle. In the
transposition depicted here, there is the formation of the IV
septum. For survival of the infant, it is necessary that there also
be either an interatrial septal defect or a patent ductus arteriosus.
Figure 9
III. In figure 10 there is complete transposition of the great
vessels with an interventricular septal defect. The aorta arises
from the right ventricle. The pulmonary artery arises from the
left ventricle. This defect is due to the improper spiraling of
the aorticopulmonary septum that normally occurs during
development.
Figure 10
IV. In figure 11, there is incomplete transposition of the great
vessels with both arising from the right ventricle. In this case
the transposition occurs due to the improper spiraling of the aorticopulmonary septum. The
improper position of the great vessels results from the lack of a leftward shift of these vessels
that normally occurs during development. Thus, there is an accompanying IV septal defect
that occurs with the improper alignment of the aorticopulmonary septum with the IV septum.
Figure 11
A vascular stenosis is a narrowing of one of the arteries.
Developmentally, a stenosis can be the result of many different
factors. When a stenosis occurs during development it not only
results in a defect of the vessel itself, but also can produce
hypertrophy or hyperplasia of the accompanying ventricle.
V. In the case seen in figure 12, there is a subvalvular aortic
stenosis. This can be due to an abnormal increase in connective
tissue or muscular tissue in the region. The reason for the increase
in tissue may range from abnormal mitral valve formation to
improper development of the annulus fibrosus in that region. In
this case of aortic stenosis there could be an accompanying
hypoplastic left ventricle that results in hypertrophy of the
muscular left ventricular wall and a small left ventricular chamber.
Figure 12
VI. Other types of stenosis include supravalvular aortic stenosis that can occur
anywhere along the length of the aorta. Another type of stenosis is the valvular
aortic stenosis. In this case the aortic valves can be malformed and result in the
narrowing of the outflow tract. This can happen to the pulmonary outflow tract as
well.
VII. Another type of stenosis is due to the unequal partitioning of
the aorta and pulmonary artery so that one vessel lumen is too
small. The most common syndrome that results from this type
of stenosis is Tetralogy of Fallot (Fig. 13). Here the unequal
partitioning of the aorta and pulmonary artery leaves the
pulmonary artery narrowed. This then results in the classic 4
characteristics of Tetralogy of Fallot:
1. pulmonary stenosis;
2. failure of the aorta to shift to the left so that it comes
to lie over the IV septum;
3. IV septal defect;
4. right ventricular hypertrophy due to the narrowing of
the right ventricular outflow tract.
Figure 13
Other defects of the heart and great vessels occur and their complexity and variety
go beyond the scope of this course. Due to improved clinical approaches to congenital
heart disease many of these defects are now being detected earlier and being surgically
corrected with increased success.
Major Vessels - Arteries
I. The most common defect of the cardiovascular system is the patent ductus
arteriosus. This occurs when the ductus arteriosus fails to close during the few
weeks after birth. It is now known that the closure of the ductus arteriosus, which is
functionally closed normally 15 to 20 hours after birth, is mediated by an increased
partial pressure of O2 in the blood that occurs shortly after birth. In addition,
bradykinins released from the lungs may also play a role in the closure of the
ductus. Prior to birth the dilation of the fetal vasculature is under the control of
prostaglandins. Prostaglandins relax the musculature of the wall of the ductus. In
some cases of patent ductus arteriosus, administration of inhibitors of
prostaglandins can result in the closure of the ductus.
II. Another type of defect is coarctation of the aorta. This is the
narrowing of the aorta, which is often the result of a persistence of
muscular tissue in the region of the ligamentus arteriosus. Most of
the coarctations occur in the region opposite the ductus arteriosus
and are called juxtaductal coarctation. Some can occur distal to
the ductus, while others occur proximal to the ductus, and are
called postductal and preductal, respectively.
III. At times there can be the retention of the right dorsal aorta
between the right subclavian artery (which arose in part from the
7th intersegmental artery) and the left dorsal aorta. In this case
there is the formation of the double aortic arch pictured in figure
14. This may be entirely compatible with life.
Figure 14
IV. In another type of defect the arch of the aorta forms from the 4th
aortic arch on the right and a mirror image of the normal
development of the arch of the aorta occurs. In this case the
descending aorta forms on the right and the brachiocephalic artery is
on the left. This is depicted in figure 15 and as seen can occur with
the aorta normally arising from the left ventricle. This is a defect in
the aortic arch formation and not the bulbus cordis. It is now
thought that neural crest tissue contributes to the formation of the
aortic arches and this region and so these defects may be the result
of abnormal neural crest migration.
Figure 15
V. Other abnormalities that occur in the formation of the arteries
include the formation of a right aortic arch with a
retroesophageal left subclavian artery (Fig. 16). In this case
the left subclavian lies posterior to the esophagus and may
actually constrict it. Another abnormality is a normal left
aortic arch with an anomalous right subclavian artery which
arises from the retained right dorsal aorta.
Figure 16
Major Vessels - Veins
As noted previously, there are many variations in the location of the large veins.
This is the result of the fact that the veins often develop in a variety of patterns. An
example is the position of the portal vein, superior mesenteric vein, inferior mesenteric
vein, and the splenic vein. Therefore, many variations in the development of the veins
are completely compatible with life. There are some examples that are worth mentioning
for this discussion.
a.
One example is the double superior vena cava. This is due to the complete retention
of the left anterior and common cardinal veins. It may or may not be accompanied by
the remnants of the thymico-thyroid anastomosis of veins with the larger vessel the
remnant of the thymico-thyroid veins (called the bridging vein) the smaller vessel,
the left superior vena cava.
i.
In the case in figure 17, the left superior vena cava empties into the right
atrium.
ii. However, in the case in figure 18, the left superior vena cava arises from the
left atrium.
Anomalies of the inferior vena cava and its tributaries also occur.
Figure 17
b.
Figure 18
Finally, pulmonary vein anomalies also occur and there are many variations. In some
cases the anomalous pulmonary veins can enter the right atrium, though most often
not directly. Again sophisticated imaging techniques have allowed for better
detection of many of these variations.